Comparative Systems Biology of the Sporulation Initiation Network in Prokaryotes

Many years of experimental and computational molecular biology of model organisms such as Escherichia coli and Saccharomyces cerevisiae has elucidated the gene regulatory network in these organisms. Relatively little is known about gene regulation in species other than the model organisms, whether gene regulatory networks are conserved, and to what degree our knowledge based on model organisms reflects biological networks occurring in nature as a whole. In this paper, we describe a first attempt to understand the gene regulatory network in lesser-known organisms, using our knowledge of gene regulation in a well-understood model organism. Such an extrapolation is particularly valuable in the study of disease-causing infectious agents, as well as other organisms that are difficult to grow or handle in a laboratory environment. In addition, comparative systems biology can identify which parts of biological networks are poorly understood and are therefore promising venues for further experimental research. We analyze the gene regulatory network responsible for the initiation of sporulation in fourteen target organisms, using Bacillus subtilis as the model organism. Instead of focusing on individual transcription factor binding sites, we devise a scoring function that takes into account the effect of multiple transcription factors binding to the regulatory region. Whereas the core gene regulatory network appears to be conserved, the degree of conservation decreases rapidly for more remote organisms, as well as for regulatory relations in the periphery of the network. Our work shows that gene regulation is still poorly understood in species other than the model organisms.